Tissue sampling and catheter selection cancer treatment methods

ABSTRACT

A catheter treatment apparatus comprises an elongate tubular member and an expandable support. The expandable support comprises a radioactive substance to treat cancerous tissue and is configured to expand from a narrow profile for insertion to a wide profile to engage and treat tissue remaining after resection. The expandable support can be sized to fit within a volume of removed tissue to place the radioactive substance in proximity to the capsule and remaining tissue, to spare the capsule and proximate nerves and vessels to treat tissue in proximity to the capsule. The elongate tubular member may comprise a channel such as a lumen to pass a bodily fluid such as urine when the expandable support engages the tissue to treat the patient for a plurality of days. The treatment apparatus can be used to resect and diagnose tissue concurrently. Based on the diagnosis, targeted segmental treatment may be given.

RELATED APPLICATIONS

The present application is a divisional application of U.S. patentapplication Ser. No. 15/587,336, filed May 4, 2017, now U.S. Pat. No.10,369,380, issued Aug. 6, 2019, which is a continuation of U.S. patentapplication Ser. No. 15/388,449, filed on Dec. 22, 2016, now U.S. Pat.No. 10,016,620, issued Jul. 10, 2018, which is a bypass continuation ofInternational Application No. PCT/US2015/037,521, filed Jun. 24, 2015,which claims priority to U.S. Provisional Patent Application No.62/016,589, filed Jun. 24, 2014, to U.S. Provisional Patent ApplicationNo. 62/018,359, filed Jun. 27, 2014, and to U.S. Provisional PatentApplication No. 62/046,274, filed Sep. 5, 2014, the entire disclosuresof which are incorporated herein by reference.

The subject matter of this PCT application is related to andincorporates by references the complete disclosures of the followingcommonly owned U.S. patents and applications: U.S. application Ser. No.12/700,568, filed Feb. 4, 2010, now U.S. Pat. No. 9,232,959, issued Jan.12, 2016, U.S. Provisional Application No. 61/874,849, filed Sep. 6,2014, U.S. Provisional Application No. 61/972,730, filed Mar. 31, 2014,and U.S. Provisional Application No. 62/019,305, filed Jun. 30, 2014.

The subject matter of this PCT application is also related toInternational Application No. PCT/US2013/028,441, filed 28 Feb. 2013,published as WO2013130895 on Sep. 6, 2013, and to InternationalApplication No. PCT/US2011/023,781, filed on Feb. 4, 2011, published asWO2011097505 on Nov. 8, 2011, the full disclosure of which isincorporated herein by reference.

BACKGROUND

The field of the present invention is related to tissue sample and thetreatment of cancer tissue, and more specifically to the tissue samplingand treatment of an organ such as the prostate.

Prior methods and apparatus of treating subjects such as patients canresult in less than ideal results in at least some instances. Forexample, prior methods of prostate surgery can result in longer healingtime and less than ideal outcomes in at least some instances.

Many organs such as the prostate comprise an outer wall or capsule,which comprises sensitive nerves or blood vessels. Damage to the nervesor vessels can lead to decreased functioning of the organ, and the priormethods and apparatus can provide less than ideal removal of tissue nearcapsules and walls of organs. For example, damage to nerves of theprostate capsule may lead to decreased potency, and damage to the opticnerve or vessels of the eye can lead to decreased vision in at leastsome instances.

Also, the prior methods and apparatus for sampling of tissue to collectcells may result in less ideal results in at least some instances.

In light of the above, it would be helpful to provide improved methodsand apparatus for surgery and treating cancer. Ideally such methodswould provide improved treatment near delicate tissue structures such asnerves and vessels of the organ with improved outcomes.

The field of the present invention is related to the sampling of cellsand tissue and treatment of tissue, and more specifically to thesampling and treatment of an organ such as the prostate.

Although early diagnosis and treatment of cancer can provide improvedoutcomes, the prior methods and apparatus of diagnosing and treatingcancer can be less than ideal. In at least some instances, patientshaving benign prostate hyperplasia (BPH) may also have prostate cancer(PCa), which may not be diagnosed as quickly as would be ideal. Also,the prior methods and apparatus for treating cancer may be less thanideally suited for combination with other treatments, for example.

In light of the above, it would be helpful to provide improved methodsand apparatus for surgery and diagnosing and treating cancer. Ideallysuch methods would provide improved treatment of delicate tissuestructures such as nerves and vessels of the organ, and determine thepresence or absence of cancer and provide improved treatments withimproved outcomes.

SUMMARY

Embodiments of the present invention provide improved methods andapparatus for the treatment of patients who may be at risk for cancer,and are well suited for combination with surgical treatments such astissue resection. The resected tissue may comprise hyperplasia of anorgan having a capsule such as the prostate, in which delicate vesselsand nerves are located proximate the capsule. The embodiments disclosedherein can treat tissue near the capsule with decreased damage to thecapsule and adjacent tissue structures such as blood vessels and nerves.In many embodiments, a catheter treatment apparatus comprises anelongate tubular member and an expandable support sized together toplace the expandable support in the treated organ. In many embodiments,the expandable support comprises a radioactive substance to treatcancerous tissue, and the expandable support is configured to expandfrom a narrow profile configuration for insertion to a wide profileconfiguration to in order to engage and treat tissue remaining afterresection. The expandable support can be sized to fit within a volume ofremoved tissue in order to place the radioactive substance in proximityto the capsule and remaining tissue, in order to spare the capsule andproximate nerves and vessels in order treat tissue in proximity to thecapsule. The elongate tubular member may comprise a channel such as alumen to pass a bodily fluid such as urine when the expandable supportengages the tissue in order to treat the patient for a plurality ofdays. In many embodiments, a second catheter without a radioactivesubstance is provided to the physician, and the patient treated with thecatheter having the radioactive substance or the second catheter withoutthe radioactive substance.

The expandable support can be configured in one or more of many ways toposition the support in proximity to the remaining tissue, and maycomprise a balloon, or a plurality of expandable struts, andcombinations thereof. The elongate tubular member may comprise aplurality of internal channels, such as a first lumen and a secondlumen, in which the first lumen comprises a longitudinal length andcross-sectional width in order to allow passage of the bodily fluid, andthe second lumen comprises a longitudinal length and a cross-sectionalwidth in order to fill the balloon. In many embodiments, the expandablesupport is configured to retract to a narrow profile configuration forremoval when the support has been placed for a plurality of days.

The radioactive substance can be placed on the support in one or more ofmany ways in order to treat the tissue, and may comprise one or more ofseeds, barbs, a fluid, or a layer of radioactive material. In manyembodiments, the radioactive substance comprises a plurality ofradioactive seeds placed at a plurality of locations on the expandablesupport. The radioactive seeds may be located in pockets of the supportin order to retract with the support for removal with the support. Theradioactive seeds may comprise a size and number sufficient to deliver adosage of radiation to the patient with a radiation treatment profilewhen placed for a plurality of days, and the seeds can be spaced aparton the support with the expanded profile configuration in order toprovide the radiation treatment profile when the support comprises theexpanded profile configuration. In many embodiments, the seeds arespaced apart on the support with substantially uniform distances over atleast a portion of the support in order to provide a substantiallyuniform treatment profile. The placement of the seeds in proximity tothe capsule can allow for treatment of hyperplasia near the capsulewithout penetrating the capsule. Alternatively, the radioactivesubstance may comprise a plurality of barbs released from the supportwhen the support expands for implantation in the patient, and the barbscan be sized to avoid penetration of the capsule or to penetrate thecapsule as appropriate. In many embodiments, the physician is providedwith a plurality of three catheters, and one of the catheters insertedinto the patient in response to testing of the resected tissue samplecollected from the patient. Alternatively, a catheter without theradioactive material can be provided to the physician, and the physiciancan inject the radioactive substance, for example with filling of theballoon with the radioactive substance.

While embodiments of the present invention are specifically directed attransurethral treatment of the prostate, certain aspects of theinvention may also be used to treat and modify other organs such asbrain, heart, lungs, intestines, eyes, skin, kidney, liver, pancreas,stomach, uterus, ovaries, testicles, bladder, ear, nose, mouth, softtissues such as bone marrow, adipose tissue, muscle, glandular andmucosal tissue, spinal and nerve tissue, cartilage, hard biologicaltissues such as teeth, bone, as well as body lumens and passages such asthe sinuses, ureter, colon, esophagus, lung passages, blood vessels, andthroat. The devices disclosed herein may be inserted through an existingbody lumen, or inserted through an opening created in body tissue.

Embodiments of the present invention provide improved methods andapparatus for the treatment of patients who may be at risk for cancer,and are well suited for combination with surgical treatments such astissue resection. The resected tissue may comprise hyperplasia of anorgan having a capsule such as the prostate, in which delicate vesselsand nerves are located proximate the capsule. The embodiments disclosedherein can treat tissue near the capsule with decreased damage to thecapsule and adjacent tissue structures such as blood vessels and nerves.In many embodiments, a catheter treatment apparatus comprises anelongate tubular member and an expandable support sized together toplace the expandable support in the treated organ. In many embodiments,the expandable support comprises a radioactive substance to treatcancerous tissue, and the expandable support is configured to expandfrom a narrow profile configuration for insertion to a wide profileconfiguration to in order to engage and treat tissue remaining afterresection. The expandable support can be sized to fit within a volume ofremoved tissue in order to place the radioactive substance in proximityto the capsule and remaining tissue, in order to spare the capsule andproximate nerves and vessels in order treat tissue in proximity to thecapsule. The elongate tubular member may comprise a channel such as alumen to pass a bodily fluid such as urine when the expandable supportengages the tissue in order to treat the patient for a plurality ofdays. In many embodiments, a second catheter without a radioactivesubstance and a diagnostic test from a surgical tissue sample isprovided to the physician, and the patient treated with the catheterhaving the radioactive substance or the second catheter without theradioactive substance in response to the diagnostic test.

The expandable support can be configured in one or more of many ways toposition the support in proximity to the remaining tissue, and maycomprise a balloon, or a plurality of expandable struts, andcombinations thereof. The elongate tubular member may comprise aplurality of internal channels, such as a first lumen and a secondlumen, in which the first lumen comprises a longitudinal length andcross-sectional width in order to allow passage of the bodily fluid, andthe second lumen comprises a longitudinal length and a cross-sectionalwidth in order to fill the balloon. In many embodiments, the expandablesupport is configured to retract to a narrow profile configuration forremoval when the support has been placed for a plurality of days.

The radioactive substance can be placed on the support in one or more ofmany ways in order to treat the tissue, and may comprise one or more ofseeds, barbs, a fluid, or a layer of radioactive material. In manyembodiments, the radioactive substance comprises a plurality ofradioactive seeds placed at a plurality of locations on the expandablesupport. The radioactive seeds may be located in pockets of the supportin order to retract with the support for removal with the support. Theradioactive seeds may comprise a size and number sufficient to deliver adosage of radiation to the patient with a radiation treatment profilewhen placed for a plurality of days, and the seeds can be spaced aparton the support with the expanded profile configuration in order toprovide the radiation treatment profile when the support comprises theexpanded profile configuration. In many embodiments, the seeds arespaced apart on the support with substantially uniform distances over atleast a portion of the support in order to provide a substantiallyuniform treatment profile. The placement of the seeds in proximity tothe capsule can allow for treatment of hyperplasia near the capsulewithout penetrating the capsule. Alternatively, the radioactivesubstance may comprise a plurality of barbs released from the supportwhen the support expands for implantation in the patient, and the barbscan be sized to avoid penetration of the capsule or to penetrate thecapsule as appropriate. In many embodiments, the physician is providedwith a plurality of three catheters, and one of the catheters insertedinto the patient in response to testing of the resected tissue samplecollected from the patient. Alternatively, a catheter without theradioactive material can be provided to the physician, and the physiciancan inject the radioactive substance, for example with filling of theballoon with the radioactive substance.

While embodiments of the present invention are specifically directed attransurethral treatment of the prostate, certain aspects of theinvention may also be used to treat and modify other organs such asbrain, heart, lungs, intestines, eyes, skin, kidney, liver, pancreas,stomach, uterus, ovaries, testicles, bladder, ear, nose, mouth, softtissues such as bone marrow, adipose tissue, muscle, glandular andmucosal tissue, spinal and nerve tissue, cartilage, hard biologicaltissues such as teeth, bone, as well as body lumens and passages such asthe sinuses, ureter, colon, esophagus, lung passages, blood vessels, andthroat. The devices disclosed herein may be inserted through an existingbody lumen, or inserted through an opening created in body tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

A better understanding of the features and advantages of the presentdisclosure will be obtained by reference to the following detaileddescription that sets forth illustrative embodiments, in which theprinciples of the disclosure are utilized, and the accompanying drawingsof which:

FIG. 1 is a schematic illustration of a device suitable for performingintraurethral prostatic tissue debulking in accordance with embodiments;

FIGS. 2A-2D illustrate use of the device of FIG. 1 in performingprostatic tissue debulking;

FIGS. 3A and 3B show a system to treat a patient in accordance withembodiments;

FIG. 4A shows pressure regulation of the surgical site with asubstantially constant pressure and variable flow, in accordance withembodiments;

FIG. 4B shows flow regulation of the surgical site with a pump providinga substantially fixed fluidic flow and a substantially constantpressure, in accordance with embodiments;

FIG. 5A shows an organ suitable for incorporation in accordance withmany embodiments;

FIG. 5B shows the prostate of FIG. 5A treated with an apparatus inaccordance with many embodiments;

FIG. 5C shows tissue of the organ treated with radiation with anexpandable support and radiation therapy in accordance with manyembodiments;

FIG. 5D shows an ablative flame visible to the human eye, in accordancewith embodiments;

FIG. 5E shows a high speed image of the ablative flame as in FIG. 5C;

FIG. 5F shows a plurality of shedding pulses and sweeping of theablative jet to provide smooth and controlled tissue erosion at aplurality of overlapping locations in accordance with embodiments;

FIG. 6A shows a treatment apparatus in accordance with many embodiments;

FIG. 6B shows internal end in a narrow profile configuration inaccordance with many embodiments;

FIG. 6C shows the internal end in an expanded wide profile configurationin accordance with many embodiments;

FIG. 7A shows a radioactive substance comprising a barb configured topenetrate tissue in accordance with many embodiments;

FIG. 7B shows barb configured for retraction from the tissue inaccordance with many embodiments;

FIG. 7C shows a radioactive seed embedded in the expandable support inaccordance with embodiments;

FIG. 7D shows a radioactive seed retained in a pocket of the support inaccordance with embodiments;

FIG. 8A is a treatment apparatus comprising an anchor in accordance withmany embodiments;

FIG. 8B shows expandable support and anchor structure in an expandedconfiguration in accordance with many embodiments;

FIG. 9 shows a treatment apparatus in accordance with many embodiments;

FIG. 10 shows apparatus in accordance with many embodiments;

FIG. 11 shows apparatus comprising expandable support and anchor inaccordance with many embodiments;

FIG. 12 shows cautery electrodes on an expandable support in accordancewith many embodiments;

FIG. 13 shows an expandable support comprising a plurality oflongitudinal struts and a plurality of transverse members in accordancewith many embodiments;

FIG. 14A shows a treatment apparatus comprising a bladder drain port,urine exit port, and inflation port in a narrow profile configuration inaccordance with many embodiments;

FIG. 14B shows apparatus in an expanded configuration in accordance withmany embodiments;

FIGS. 15A and 15B show a treatment apparatus comprising a sub-layerballoon and a treatment substance port in an expanded configuration inaccordance with many embodiments;

FIG. 16 shows a treatment apparatus comprising a peripheral isolationballoon in an expanded configuration in accordance with manyembodiments;

FIGS. 17A1 and 17A2 show a treatment apparatus comprising radioactivepellets in accordance with many embodiments;

FIG. 17B shows the structure of radioactive pellets and method forconfiguration in accordance with many embodiments;

FIG. 18 shows an expandable support comprising a plurality of shapes inaccordance with many embodiments;

FIG. 19 shows bipolar cautery electrodes on an expandable support inaccordance with many embodiments;

FIG. 20 shows a method of treating a patient in accordance with manyembodiments;

FIGS. 21A and 21B show sectional views of a treatment apparatus in useto treat a patient in accordance with many embodiments;

FIGS. 21C and 21D show transverse views of the prostate divided intotissue collection zones;

FIG. 22 shows maximum tissue penetration depth of cutting and flow ratethrough a nozzle in accordance with embodiments; and

FIG. 23 shows selective removal of potato with a porcine blood vesselpositioned over the incision of the potato as a model for selectiveremoval of tissue.

DETAILED DESCRIPTION

A better understanding of the features and advantages of the presentdisclosure will be obtained by reference to the following detaileddescription that sets forth illustrative embodiments, in which theprinciples of embodiments of the invention are utilized, and theaccompanying drawings.

Although the detailed description contains many specifics, these shouldnot be construed as limiting the scope of the invention but merely asillustrating different examples and aspects of the invention. It shouldbe appreciated that the scope of the invention includes otherembodiments not discussed in detail above. Various other modifications,changes and variations which will be apparent to those skilled in theart may be made in the arrangement, operation and details of the methodand apparatus of the present invention disclosed herein withoutdeparting from the spirit and scope of the invention as describedherein.

The embodiments as disclosed herein can be used to collect fat cells andprostate tissue, and many other tissue types of tissue, such as tissuefrom other organs, for example.

The embodiments disclosed herein can be combined in one or more of manyways to provide improved therapy to a patient. The disclosed embodimentscan be combined with prior methods and apparatus to provide improvedtreatment, such as combination with known methods of prostate surgeryand surgery of other tissues and organs, for example. It is to beunderstood that any one or more of the structures and steps as describedherein can be combined with any one or more additional structures andsteps of the methods and apparatus as described herein, the drawings andsupporting text provide descriptions in accordance with embodiments.Methods and apparatus of tissue removal suitable for incorporation inaccordance with embodiments as disclosed herein are described in:PCT/US2013/028441, filed 28 Feb. 2013; U.S. Provisional Application No.61/874,849, filed Sep. 6, 2014; U.S. Provisional Application No.61/972,730, filed Mar. 31, 2014; the entire disclosures of which havebeen previously incorporated herein by reference.

Although the treatment planning and definition of treatment profiles andvolumes as described herein are presented in the context of prostatesurgery, the methods and apparatus as described herein can be used totreat any tissue of the body and any organ and vessel of the body suchas brain, heart, lungs, intestines, eyes, skin, kidney, liver, pancreas,stomach, uterus, ovaries, testicles, bladder, ear, nose, mouth, softtissues such as bone marrow, adipose tissue, muscle, glandular andmucosal tissue, spinal and nerve tissue, cartilage, hard biologicaltissues such as teeth, bone, etc. as well as body lumens and passagessuch as the sinuses, ureter, colon, esophagus, lung passages, bloodvessels and throat.

As used herein, A and/or B encompasses A alone, B alone, andcombinations of A and B together.

As used herein, the term Aquablation™ encompasses ablation with water.

As used herein, the words telescope, endoscope and cytoscope are usedinterchangeably.

As used herein, the terms entrainment region and cavitation region areused interchangeably.

As used herein, a non-radioactive substance encompasses a substancewhich may have trace amounts of background radiation but which does nothave enough radiation to provide a treatment.

The imaging and treatment probes as described herein can be combined inone or more of many ways, and in many embodiments the images of thepatient can be used to define a target volume and a target profile ofthe volume of tissue removed. The profile of tissue removed can beplanned to efficaciously remove tissue. The methods and apparatus forimaging as described herein can be used to beneficially plan fortreatment. Alternatively or in combination, the imaging methods andapparatus as described herein can be used to modify the treatment inreal time as the patient is treated, for example.

The visible entrainment and cavitation region can be combined with theimages of tissue and treatment regions shown on the display, so as toprovide confirmation that the correct amount of tissue will be resected.In many embodiments, the distance of the visible entrainment regioncorresponds to a maximum cut depth, such that the surgeon can select thedepth of the cut based on images and with adjustment of treatmentparameters such as one or more of flow rate, nozzle diameter, orpressure.

The visible entrainment region as described herein comprises region ofcavitation of the fluid stream emitted from the energy source such as anozzle, and the maximum resection depth corresponds to the distance ofthe visible entrainment region. By visible entrainment region, it ismeant that the user can visualize the entrainment region with imagingsensitive to formation of cavitation pockets, such as visible andultrasound imaging which scatter waves in response to cavitation pocketsbeing formed.

As used herein a processor encompasses one or more processors, forexample a single processor, or a plurality of processors of adistributed processing system for example. A controller or processor asdescribed herein generally comprises a tangible medium to storeinstructions to implement a steps of a process, and the processor maycomprise one or more of a central processing unit, programmable arraylogic, gate array logic, or a field programmable gate array, forexample.

As used herein like characters and numerals identify like elements.

As used herein, real-time a real time image shown on a displayencompasses an image shown within a few seconds of the event shown. Forexample, real time imaging of a tissue structure encompasses providingthe real time image on a display within about ten seconds of the imagebeing acquired.

As used herein, the terms distal and proximal refer to locationsreferenced from the apparatus, and can be opposite of anatomicalreferences. For example a distal location of a probe may correspond to aproximal location of an elongate member of the patient, and a proximallocation of the probe may correspond to a distal location of theelongate member of the patient.

Automated robotic control—where movement of the water jet is motorizedand under computer control with preselected routines—allows accurate andfinely detailed resections not possible with manual control. Advantagesinclude reduced time required for procedures, fewer complications,improved outcomes and less training time needed for surgeons. Many ofthese improvements arise from reducing or eliminating the need formanual dexterity of the treating physician. Automatic control furtherallows the cutting power of the nozzle to be increased to levels notachievable with full manual control. The system may be manuallycontrolled during less critical portions of the procedure, e.g. duringinitial selection of an area to operate on and for touch-ups in cuttingand cautery. Even during these less critical phases of the protocols,the increased precision and smoothness provided by the automated controlcan provide reduction and filtering of hand jitter. Another significantadvantage is that automation allows for pretesting or “dry runs” of aprocedure. When a cutting routine is selected, the limits of area can beselected using a joystick or other control element to position the laserduring a mock the procedure without cutting. Changes can be made beforecutting commences, so that errors can be corrected before beginning theactual procedure.

INCORPORATION BY REFERENCE

The subject matter of FIGS. 1 to 2D and the corresponding text have beenincorporated by reference as described in: U.S. application Ser. No.12/700,568, filed Feb. 4, 2010, now U.S. Pat. No. 9,232,959, issued Jan.12, 2016; and International Application No. PCT/US2011/023781, filed onApr. 8, 2007, published as WO2011097505 on Nov. 8, 2011; the fulldisclosures of which have been previously incorporated herein byreference.

Referring to FIG. 1, an exemplary prostatic tissue debulking device 10constructed in accordance with the principles of the present inventioncomprises a catheter assembly generally including a shaft 12 having adistal end 14 and a proximal end 16. The shaft 12 will typically be apolymeric extrusion including one, two, three, four, or more axiallumens extending from a hub 18 at the proximal end 16 to locations nearthe distal end 14. The shaft 12 will generally have a length in therange from 15 cm to 25 cm and a diameter in the range from 1 mm to 10mm, usually from 2 mm to 6 mm. The shaft will have sufficient columnstrength so that it may be introduced upwardly through the male urethra,as described in more detail below.

The shaft will include an energy source positioned in the energydelivery region 20, where the energy source can be any one of a numberof specific components as discussed in more detail below. Distal to theenergy delivery region, an inflatable anchoring balloon 24 will bepositioned at or very close to the distal end 14 of the shaft. Theballoon will be connected through one of the axial lumens to a ballooninflation source 26 connected through the hub 18. In addition to theenergy source 22 and the balloon inflation source 26, the hub willoptionally further include connections for an infusion/flushing source28, an aspiration (a vacuum) source 30, and/or an insufflation(pressurized C02 or other gas) source 32. In the exemplary embodiment,the infusion or flushing source 28 can be connected through an axiallumen (not shown) to one or more delivery ports 34 proximal to theballoon anchor 24 and distal to the energy delivery region 20. Theaspiration source 30 can be connected to a second port or opening 36,usually positioned proximally of the energy delivery region 20, whilethe insufflation source 32 can be connected to an additional port 38,also usually located proximal of the energy delivery region. It will beappreciated that the locations of the ports 34, 36, and 38 are notcritical, although certain positions may result in particular advantagesdescribed herein, and that the lumens and delivery means could beprovided by additional catheters, tubes, and the like, for exampleincluding coaxial sleeves, sheathes, and the like which could bepositioned over the shaft 12.

While the present embodiments are described with reference to the humanprostate, it is understood that they may be used to treat mammalprostates in general. Referring now to FIGS. 2A-2D, the prostatic tissuedebulking device 10 is introduced through the male urethra U to a regionwithin the prostate P which is located immediately distal to the bladderB. The anatomy is shown in FIG. 2A. Once the catheter 10 has beenpositioned so that the anchoring balloon 24 is located just distal ofthe bladder neck BN (FIG. 2B) the balloon can be inflated, preferably tooccupy substantially the entire interior of the bladder, as shown inFIG. 2C. Once the anchoring balloon 24 is inflated, the position of theprostatic tissue debulking device 10 will be fixed and stabilized withinthe urethra U so that the energy delivery region 20 is positioned withinthe prostate P. It will be appreciated that proper positioning of theenergy delivery region 20 depends only on the inflation of the anchoringballoon 24 within the bladder. As the prostate is located immediatelyproximal to the bladder neck BN, by spacing the distal end of the energydelivery region very close to the proximal end of the balloon, typicallywithin the range from 0 mm to 5 mm, preferably from 1 mm to 3 mm, thedelivery region can be properly located. After the anchoring balloon 24has been inflated, energy can be delivered into the prostate fordebulking, as shown by the arrows in FIG. 2. Once the energy has beendelivered for a time and over a desired surface region, the energyregion can be stopped and the prostate will be debulked to relievepressure on the urethra, as shown in FIG. 2D. At that time, a flushingfluid may be delivered through port 34 and aspirated into port 36, asshown in FIG. 2D. Optionally, after the treatment, the area could becauterized using a cauterizing balloon and/or stent which could beplaced using a modified or separate catheter device.

FIGS. 3A and 3B show a system to treat a patient in accordance withembodiments. The system 400 comprises a treatment probe 450 and mayoptionally comprise an imaging probe 460. The treatment probe 450 iscoupled to a console 420 and a linkage 430. The imaging probe 460 iscoupled to an imaging console 490. The patient treatment probe 450 andthe imaging probe 460 can be coupled to a common base 440. The patientis supported with the patient support 449. The treatment probe 450 iscoupled to the base 440 with an arm 442. The imaging probe 460 iscoupled to the base 440 with an arm 444.

The patient is placed on the patient support 449, such that thetreatment probe 450 and ultrasound probe 460 can be inserted into thepatient. The patient can be placed in one or more of many positions suchas prone, supine, upright, or inclined, for example. In manyembodiments, the patient is placed in a lithotomy position, and stirrupsmay be used, for example. In many embodiments, the treatment probe 450is inserted into the patient in a first direction on a first side of thepatient, and the imaging probe is inserted into to the patient in asecond direction on a second side of the patient. For example, thetreatment probe can be inserted from an anterior side of the patientinto a urethra of the patient, and the imaging probe can be insertedtrans-rectally from a posterior side of the patient into the intestineof the patient. The treatment probe and imaging probe can be placed inthe patient with one or more of urethral tissue, urethral wall tissue,prostate tissue, intestinal tissue, or intestinal wall tissue extendingtherebetween.

The treatment probe 450 and the imaging probe 460 can be inserted intothe patient in one or more of many ways. During insertion, each arm maycomprise a substantially unlocked configuration such the probe can bedesirably rotated and translated in order to insert the probe into tothe patient. When a probe has been inserted to a desired location, thearm can be locked. In the locked configuration, the probes can beoriented in relation to each other in one or more of many ways, such asparallel, skew, horizontal, oblique, or non-parallel, for example. Itcan be helpful to determine the orientation of the probes with anglesensors as described herein, in order to map the image date of theimaging probe to treatment probe coordinate references. Having thetissue image data mapped to treatment probe coordinate reference spacecan allow accurate targeting and treatment of tissue identified fortreatment by an operator such as the physician.

In many embodiments, the treatment probe 450 is coupled to the imagingprobe 460. In order to align the treatment with probe 450 based onimages from imaging probe 460. The coupling can be achieved with thecommon base 440 as shown. Alternatively or in combination, the treatmentprobe and/or the imaging probe may comprise magnets to hold the probesin alignment through tissue of the patient. In many embodiments, the arm442 is a movable and lockable arm such that the treatment probe 450 canbe positioned in a desired location in a patient. When the probe 450 hasbeen positioned in the desired location of the patient, the arm 442 canbe locked with an arm lock 427. The imaging probe can be coupled to base440 with arm 444, can be used to adjust the alignment of the probe whenthe treatment probe is locked in position. The arm 444 may comprise alockable and movable probe under control of the imaging system or of theconsole and of the user interface, for example. The movable arm 444 maybe micro-actuable so that the imaging probe 440 can be adjusted withsmall movements, for example a millimeter or so in relation to thetreatment probe 450.

In many embodiments the treatment probe 450 and the imaging probe 460are coupled to angle sensors so that the treatment can be controlledbased on the alignment of the imaging probe 460 and the treatment probe450. An angle sensor 495 is coupled to the treatment probe 450 with asupport 438. An angle sensor 497 is coupled to the imaging probe 460.The angle sensors may comprise one or more of many types of anglesensors. For example, the angle sensors may comprise goniometers,accelerometers and combinations thereof. In many embodiments, anglesensor 495 comprises a 3-dimensional accelerometer to determine anorientation of the treatment probe 450 in three dimensions. In manyembodiments, the angle sensor 497 comprises a 3-dimensionalaccelerometer to determine an orientation of the imaging probe 460 inthree dimensions. Alternatively or in combination, the angle sensor 495may comprise a goniometer to determine an angle of treatment probe 450along an elongate axis of the treatment probe. Angle sensor 497 maycomprise a goniometer to determine an angle of the imaging probe 460along an elongate axis of the imaging probe 460. The angle sensor 495 iscoupled to a controller 424. The angle sensor 497 of the imaging probeis coupled to a processor 492 of the imaging system 490. Alternatively,the angle sensor 497 can be coupled to the controller 424 and also incombination.

The console 420 comprises a display 425 coupled to a processor system incomponents that are used to control treatment probe 450. The console 420comprises a processor 423 having a memory 421. Communication circuitry422 is coupled to processor 423 and controller 424. Communicationcircuitry 422 is coupled to the imaging system 490. The console 420comprises components of an endoscope 426 is coupled to anchor 24.Infusion flashing control 28 is coupled to probe 450 to control infusionand flushing. Aspiration control 30 is coupled to probe 450 to controlaspiration. Endoscope 426 can be components of console 420 and anendoscope insertable with probe 450 to treat the patient. Arm lock 427of console 420 is coupled to arm 422 to lock the arm 422 or to allow thearm 422 to be freely movable to insert probe 450 into the patient.

The console 420 may comprise a pump 419 coupled to the carrier andnozzle as described herein.

The processor, controller and control electronics and circuitry caninclude one or more of many suitable components, such as one or moreprocessor, one or more field-programmable gate array (FPGA), and one ormore memory storage devices. In many embodiments, the controlelectronics controls the control panel of the graphic user interface(hereinafter “GUI”) to provide for pre-procedure planning according touser specified treatment parameters as well as to provide user controlover the surgery procedure.

The treatment probe 450 comprises an anchor 24. The anchor 24 anchorsthe distal end of the probe 450 while energy is delivered to energydelivery region 20 with the probe 450. The probe 450 may comprise anozzle 200 as described herein. The probe 450 is coupled to the arm 422with a linkage 430.

The linkage 430 comprises components to move energy delivery region 20to a desired target location of the patient, for example, based onimages of the patient. The linkage 430 comprises a first portion 432 anda second portion 434 and a third portion 436. The first portion 432comprises a substantially fixed anchoring portion. The substantiallyfixed anchoring portion 432 is fixed to support 438. Support 438 maycomprise a reference frame of linkage 430. Support 438 may comprise arigid chassis or frame or housing to rigidly and stiffly couple arm 442to treatment probe 450. The first portion 432 remains substantiallyfixed, while the second portion 434 and third portion 436 move to directenergy from the probe 450 to the patient. The first portion 432 is fixedto the substantially constant distance 437 to the anchor 24. Thesubstantially fixed distance 437 between the anchor 24 and the fixedfirst portion 432 of the linkage allows the treatment to be accuratelyplaced. The first portion 432 may comprise the linear actuator toaccurately position the high pressure nozzle in treatment region 20 at adesired axial position along an elongate axis of probe 450.

The elongate axis of probe 450 generally extends between a proximalportion of probe 450 near linkage 430 to a distal end having anchor 24attached thereto. The third portion 436 controls a rotation angle aroundthe elongate axis. During treatment of the patient, a distance 439between the treatment region 20 and the fixed portion of the linkagevaries with a reference distance 439. The distance 439 adjusts inresponse to computer control to set a target location along the elongateaxis of the treatment probe referenced to anchor 24. The first portionof the linkage remains fixed, while the second portion 434 adjusts theposition of the treatment region along the axis. The third portion ofthe linkage 436 adjusts the angle around the axis in response tocontroller 424 such that the distance along the axis at an angle of thetreatment can be controlled very accurately with reference to anchor 24.The probe 450 may comprise a stiff member such as a spine extendingbetween support 438 and anchor 24 such that the distance from linkage430 to anchor 24 remains substantially constant during the treatment.The treatment probe 450 is coupled to treatment components as describedherein to allow treatment with one or more forms of energy such asmechanical energy from a jet, electrical energy from electrodes oroptical energy from a light source such as a laser source. The lightsource may comprise infrared, visible light or ultraviolet light. Theenergy delivery region 20 can be moved under control of linkage 430 suchas to deliver an intended form of energy to a target tissue of thepatient.

The imaging system 490 comprises a memory 493, communication circuitry494 and processor 492. The processor 492 in corresponding circuitry iscoupled to the imaging probe 460. An arm controller 491 is coupled toarm 444 to precisely position imaging probe 460.

FIG. 4A shows pressure regulation of the surgical site with asubstantially constant pressure and variable flow. The saline bag isplaced at a height to provide substantially constant pressureregulation. The bag of saline can be placed at a height corresponding toabout 50 to 100 mm of Mercury (hereinafter “mmHg”). The saline bag iscoupled to the irrigation port as described herein. A collection bag iscoupled to one or more of the irrigation port, the aspiration port, orthe suction port as described herein. The collection bag collects tissueremoved with the water jet ablation probe 450 as described herein.

FIG. 4B shows flow fluidic regulation of the surgical site with a pumpproviding a substantially fixed fluidic flow. A pump removes fluid fromthe surgical site at a substantially fixed flow rate. The pump maycomprise a peristaltic pump, for example. The pump is configured toremove fluid at the substantially the same rate or greater thanAquablation™ saline flow rate, in order to inhibit pressure build up atthe surgical site. The peristaltic pump can be coupled to the aspirationport of the manifold comprising tissue removal port 456C as describedherein, for example. Providing the pump having the flow rate that is atleast the flow rate of the tissue ablation jet provides improve suctionas ablated tissue that might otherwise block the tissue removal openingsand channel can be subjected to greater amounts of pressure when thepump maintains the substantially fixed flow rate in order to remove thematerial that would otherwise block the channel.

The irrigation flow from the saline bag may remain open in order toprovide at least two functions: 1) maintain pressure based on the heightof the saline bag; and 2) provide a safety check valve in case theperistaltic pump is not functioning correctly as visually a person wouldsee flow entering the bag as a pink color.

In alternate embodiments, the flow of the pump comprises a variable ratein order to provide a substantially constant pressure within the patientnear the surgical site. The active sensing of pressure of the treatedorgan and variable flow rate of the pump may comprise a closed looppressure regulation system. The pump can be coupled to a sensor such asa pressure sensor, and the flow rate varied to maintain substantiallyconstant pressure. The pressure sensor can be located in one or more ofmany places such as on the treatment probe, within the aspirationchannel of the probe, in a recess of an outer surface the probe, on aninner surface of the probe coupled to the surgical site, or near theinlet to the pump on the console for example.

FIG. 5A shows an organ suitable for incorporation in accordance withembodiments. The organ may comprise one or more of many organs asdescribed herein, for example, the prostate P. In many embodiments theorgan comprises a capsule C and tissue contained within the capsule andcapsular vessels CV and nerves N located on an exterior of the capsule,for example. In many embodiments the organ comprises a prostate. Theprostate may comprise hyperplasia H such as benign prostate hyperplasiaor cancer CA and combinations thereof, for example. In many embodimentsthe hyperplasic tissue may comprise tissue located within the patient inwhich the cancer may not have been detected. In many embodimentscapsular vessels and nerves extend along an exterior surface of theprostate. In many embodiments the hyperplasic tissue can be locatedsuperiorly on the prostate. In the many embodiments the hyperplasictissue may comprise tissue of unknown specificity with respect towhether the tissue comprises cancerous tissue or benign tissue.

FIG. 5B shows the prostate P of FIG. 5A treated with an apparatus inaccordance with embodiments. In many embodiments the tissue of theprostate is removed in accordance with a tissue removal profile RP. Thetissue removal profile may comprise of predetermined tissue removalprofile based on image-guided tissue removal as described herein, forexample. Alternatively the tissue removal profile may comprise ofremoval profile of tissue removed with a handheld tissue removalapparatus. In many embodiments the tissue of the organ, such as theprostate, is removed to within the capsule C in order to decrease thedistance from the tissue removable profile to the exterior of thecapsule, for example.

In many embodiments a tissue treatment apparatus, such as a catheterhaving an expandable support, is placed within the organ in order toengage the remaining tissue that defines the removal profile and thecapsule with an expandable support.

In many embodiments the tissue within the organ is removed such that thecapsule of the organ, such as the prostate, remains intact which has theadvantage of retaining the integrity of the capsule or vessel's nerveswhich may extend around an exterior surface of the capsule. In manyembodiments this removal of the capsular tissue is inhibited in order toretain the integrity of the capsule and the corresponding tissuestructures such as capsular vessels and/or nerves. The tissue removalprofile may define a cavity corresponding to the removed tissue of theorgan such as the prostate. In many embodiments a portion of the tissuenear the capsule may comprise tissue, such as cancerous tissue or tissueidentified as having a probability of being cancerous tissue, such ashyperplasic tissue in the superior portion or other portion of theorgan. The remaining tissue can be treated in one or more of many waysas described herein. In many embodiments the remaining tissue, which maycomprise remaining hyperplasic tissue, is treated with radiation.

FIG. 5C shows tissue of the organ treated with radiation with anexpandable support and radiation therapy in accordance with embodiments.An expandable support 120 may comprise one or more of many structures toallow the support to expand from a first narrow profile configuration toa second expanded profile configuration. The expandable support 120 canbe located on a distal end of an elongate tubular member 110 such as acatheter, for example. In many embodiments the expandable support 120 isinserted into a channel to access the organ, for example urethra U, asdescribed herein. The expandable support can be inserted through anexternal opening of the urethra into the patient and, subsequently, inthe narrow profile configuration and subsequently expanded to a wideprofile configuration, as shown in FIG. 5C, in order to treat thepatient. The expandable support may comprise of balloon 122, forexample. The elongate tubular member 110 may comprise a plurality ofchannels in fluidic communication with the expandable support in adistal end of the elongate tubular member. An internal end 104 of theelongate tubular member of the treatment apparatus 100 can be insertedinto an external opening of the urethra and advance towards the bladder,for example, past the prostate such that the expandable support 120 ispositioned in the cavity provided with a treatment and removal of theorgan such as the prostate. The expandable support 120 can be inflatedfrom a narrow profile configuration to an expanded profile configurationin order to treat the remaining tissue. The remaining tissue can betreated in one or more of many ways with the expandable support. Forexample, the remaining tissue may be cauterized, treated with radiationand combinations thereof. In many embodiments the remaining tissue istreated with radiation. The radiation can be provided in one or more ofmany ways with a radioactive material. For example, the radioactivematerial may comprise seeds 132 of radioactive material 130 located onthe expandable support such that the seeds of radioactive material areurged radially outward, away from the expandable support from the narrowconfiguration to the expanded profile configuration in order to engagethe remaining tissue of the organ. The radioactive seeds and materialcan be left in engagement with the tissue of the organ for a pluralityof days, for example three to five days, depending upon the intendeddosage of radiation with the treatment. Upon completion of the treatmentthe lumen can be with—the expandable support can be retracted and theexpandable support withdrawn from the patient and a narrow profileconfiguration from the prostate and the urethra, for example.

The radiation can be provided in one or more of many ways. For example,the radiation may comprise seeds; the radiation may comprise spikes; theradiation may comprise fluid injected into a lumen of a balloon, forexample, and combinations thereof. The radioactive barbs 134, or spikes,can have the advantage of extending through the remaining tissue andthrough the exterior of the capsule in order to treat residual tissuewhich may comprise cancerous tissue at an early stage of metastases inorder to inhibit spread of the metastatic cancerous tissue. For example,cancerous tissue located on an exterior of the capsule. Alternatively,or in combination, the barbs may comprise a releasable structure suchthat the barbs can remain within the tissue when the expandable supporthas been retracted away from the tissue. In many embodiments theradiation therapy can be provided by inflating a balloon with aradioactive fluid for a plurality of days such that the radioactivefluid remains within a balloon inflated within the organ, such as theprostate, for the plurality of days. Upon completion of an intendeddosage of radiation the radioactive fluid can be removed from theballoon and the balloon and elongate tubular member 110 withdrawn fromthe patient. In many embodiments the radiation therapy can be providedwith seeds coupled to the expandable support such that the seeds are inengagement with the remaining tissue for a plurality of days. Uponcompletion of the treatment the expandable support can be retracted andthe seeds retracted with the expandable support such that the radiationtherapy is not implanted in the patient and the patient has the therapyend upon removal of the radiation with the expandable support.

The elongate tubular member 110 may comprise a first lumen 112 and asecond lumen 114, for example, in which the first lumen allows the flowof urine from the urethra to pass from an internal end 104 of theapparatus 100 to an external end 102 in which the internal end ispositioned toward the bladder from the prostate and the external end 102is positioned external to an external opening of the urethra. When theexpandable support 120 comprises the expanded configuration, urine isallowed to pass from the first lumen 112 to the external opening inorder to allow the passage of urine. The second lumen 114 can be used toinflate the expandable support, for example, in which a plurality ofopenings 119 is provided to allow the second lumen 114 to be used toinflate the expandable support. The external end 102 of the elongatetubular member can be provided with structures to allow injection andretention of the fluid filling the expandable support, such as aballoon. The expandable support can be configured to urge outwardly,away from the elongate tubular member, in order to engage the remainingtissue with at least some force in order to anchor the expandablesupport and the elongate tubular member in the prostate. Alternativelyor in combination, anchor structures can be provided which anchor thetreatment apparatus 100 to the bladder of the patient in order toinhibit stress upon the treated tissue with the expandable support 100.

The expandable support 120 can have the advantage of inhibiting bleedingand blood loss and promoting healing even when provided withoutradiation therapy, for example.

FIG. 6A shows a treatment apparatus 100 in accordance with embodiments.The treatment apparatus 100 comprises an internal end 104 and anexternal end 102. The internal end 104 is configured for advancementwithin a channel which may comprise a surgically formed channel or anaturally occurring body channel and combinations thereof. The apparatus100 comprises an elongate tubular member 110 and an expandable support120. The apparatus 100 may comprise of radioactive substance 130 locatedon an expandable support 120.

The elongate tubular member 110 may comprise a catheter, for example,and the catheter 110 may comprise a plurality of lumens, for example, afirst lumen 112 and a second lumen 114. The first lumen 112 may extendfrom the external end 102 to the internal end 104, for example, in orderto allow the passage of a bodily fluid, such as urine. The secondchannel 114 can extend from the external end 102 to the expandablesupport 130 in order to expand the expandable support 130 from a firstnarrow profile configuration to a second expanded profile, or wideprofile, configuration. The narrow profile configuration allows theexpandable support to be advanced within an internal channel or lumen ofthe patient, for example.

The apparatus 100 may comprise electrodes for electro-cautery in theexpanded profile configuration, for example.

The apparatus 100 can be injected with saline to structure 120. Forexample, balloon 122 can be injected with a non-radioactive substancesuch as saline.

FIG. 6B shows internal end 104 in a narrow profile configuration 106.The expandable support 120 comprises a radioactive substance 130. Theexpandable support 120 may comprise an expandable balloon 122. Theradioactive substance 130 may comprise a plurality of radioactive seeds132. A plurality of openings 119 provides fluidic communication of thesecond lumen 114 with the expandable balloon 122. When a fluid isinjected into the external end 102 of the elongate tubular member 110the balloon 122 is urged radially outward with fluid passing throughopenings 119.

FIG. 6C shows the internal end 104 in an expanded wide profileconfiguration 108. The expanded wide profile configuration 108 isconfigured to engage tissue with the expanded wide profile configurationand with fluid injected into second lumen 114. In the expanded wideprofile configuration the radioactive substance 130 is positioned inproximity to the remaining tissue of the organ. The radioactivesubstance 130 may comprise radioactive seeds 132 distributed at aplurality of locations on the expandable support 130.

In many embodiments the plurality of radioactive seeds are situated at aplurality of locations on the expandable support 120 in order to providea therapeutic treatment profile of radiation to the tissue. Theplurality of seeds 132 can be positioned at predetermined locations onthe support 120.

In the narrow profile configuration 106 the plurality of seeds arepositioned closer to each other than in the wide profile configuration108. In the wide profile configuration the plurality of seeds are spacedapart in order to provide a therapeutic treatment profile to the tissuenear the capsule.

FIG. 7A shows a radioactive substance 130 comprising a barb 134configured to penetrate tissue. The barb 134 comprises a first end on anouter surface of the expandable support 120. The barb 134 may comprise abase coupled to and in contact with the support 120 and a distal endcomprising a pointed tip shaped to penetrate tissue. The barb 134 cancomprise an elongate distance extending from the base to the tip and theelongate distance can be sized to penetrate the remaining tissue and thecapsule in order to position the tip outside the capsule in order totreat tissue located outside of the capsule or surface, adjacent tocapsule or vessels and nerves. Alternatively, the tip and length of thebarb can be sized to inhibit penetration of the capsule. In manyembodiments the barb 134 is configured for implantation in the tissue.The barb 134 can be releasably attached to the expandable support 120such that when the support 120 expands and barb 134 is placed in tissuethe support 120 can be retracted and leave the barb 134 in the tissue asan implant. The barb 134 can be placed on an outer surface of thesupport 120 and can be loosely coupled on the outer surface of thesupport 120 for implantation in the tissue. Alternatively, the barb 134can be affixed to the support 120, for example, with a suitable glue ormechanical fixation.

FIG. 7B shows barb 134 configured for retraction from the tissue. Theradioactive substance 130 comprising the barb 134 can be withdrawn fromthe tissue when the support 120 is retracted. While the barb 134 can beconfigured for retraction in many ways and many embodiments, the support120 is penetrated with barb 134. 136 is affixed to the barb with thehead 136 located on an interior surface of the support 120 in order toaffix the barb 134 to the support 120. The head 136 may comprise a widestructure in order to retain the barb 134 with the expandable support120, for example.

FIG. 7C shows a radioactive seed 132 embedded in the expandable support120. The radioactive seed can be molded within the support, for example,or glued within the support.

FIG. 7D shows a radioactive seed 132 retained in a pocket 124 of thesupport. The pocket 124 may comprise one or more of many structuresconfigured to retain the radioactive seed 132. For example, the pocket124 may comprise an indentation, a slit or other structure capable ofreceiving the pocket, receiving the seed 132. In many embodiments asheath 126 covers the radioactive substance 130 and the sheath can beretracted, for example. Alternatively the sheath can remain affixed overthe support 120, for example.

In many embodiments the sheath 126 can be retracted to expose a barb 134in order to implant the barb within the tissue or to allow the barb tobe advanced without contacting an internal service of a lumen such as awall of the urethra.

FIG. 8A shows a treatment apparatus comprising an anchor 140 inaccordance with embodiments. The anchor 140 may comprise of an anchoringballoon 142. The anchoring balloon 142 can be expanded with the balloon122 in accordance with embodiments described herein. The anchor 140 andexpandable support 120 comprise a narrow configuration 106 for insertionalong a channel of a patient, such as a surgically formed channel or alumen of a natural channel, such as a urethra, as described herein. Inthe narrow profile configuration the anchor 140 can be advanced to thebladder neck of the patient and anchored to the bladder neck in order toinhibit movement of the expandable support 120 when placed. The anchor140 can inhibit movement of expandable support 120 in order to promotehealing and decrease potential trauma to the tissue engaged withexpandable support 120. For example, the external end 102 can beinadvertently drawn from the patient in use and anchor structure 120 canbe tugged on and anchor 140 inhibits movement of expandable support 120.

In many embodiments, the expandable support 120 comprises theradioactive substance 130 as described herein.

FIG. 8B shows expandable support 120 and anchor structure 140 in anexpanded configuration 108. In the expanded wide profile configuration108, movement of the elongate tubular member 110 and expandable support120 is inhibited. In the expanded profile configuration the apparatus100 can be left in the patient for a plurality of days. For example, atleast two days, three days, four days or five days in order to allow forthe patent to heal and to provide treatment. The elongate tubular member110 comprises structures as described herein, such as the first channeland the second channel.

FIG. 12 shows cautery electrodes 170 on an expandable support 120 asdescribed herein. The cautery electrodes may comprise bipolar electrodes172, for example. Traces can be provided to couple the electrodes 172 toan external source of power to provide electro cautery, for example. Thesupport 120 can be provided with a radioactive material as describedherein, for example.

FIG. 13 shows an expandable support 120 comprising a plurality oflongitudinal struts 128 and a plurality of transverse members 129. Theexpandable support 120 may comprise radioactive substance 130 asdescribed herein. The plurality of longitudinal struts extendslongitudinally along the support. The plurality of longitudinal strutscan be coupled to the transverse elements to expand and retract support120 as described herein, for example.

The embodiments as disclosed herein can be used to collect fat cells andprostate tissue, and many other tissue types of tissue, such as tissuefrom other organs, for example. The embodiments as disclosed herein arewell suited to detect cancer, and can be used to detect biomarkers(natural and/or synthetic), that may react and/or interact with tumorproteins, related to triggering and/or amplification of many otherprocesses, functions, or signals indicative of malignancy and/or adegree of malignancy.

The methods and apparatus as disclosed herein are well suited for usewith many other tissues in addition to the prostate. In manyembodiments, a delayed or immediate reaction can be used for an instantdetection and diagnosis. With embodiments related to prostate tissue forexample, the sample collection and detection methods as disclosed hereinallow the surgeon to treat the prostate for cancer and tailor cancertreatment based on the diagnosis after tissue collection derived fromthe patient's BPH treatment as the patient is still at the operatingtable/chair, for example.

In many embodiments, the collected tissue can be used to identifypathological condition and histological evaluation.

As used herein, the terms AquaBeam, flame, fluid flame, fluid cloud,entrainment region, and cavitation region are used interchangeably.

An apparatus for tissue removal may comprise a nozzle configured todeliver a fluid stream, wherein the fluid stream may comprise one ormore of a liquid or a gas. A liquid fluid stream may comprise one ormore of water or saline, for example. A liquid fluid stream may beconfigured to exit the nozzle in the form a liquid ablation jet, causingcavitations in the prostate tissue and dissociating the tissue into aplurality of fragments. The liquid fluid stream can be released into aliquid in which the nozzle is immersed in order to provide cavitationwith shedding pulses as described herein. The liquid in which the nozzleis immersed may comprise one or more of water or saline, for example.

FIG. 5D shows an ablative flame visible to the human eye, in accordancewith embodiments.

FIG. 5E shows a high speed image of the ablative flame as in FIG. 5C.The image was taken at a speed of about 1/400 of a second.

The data of FIGS. 5D and 5E show that the ablative flame comprises aplurality of white clouds generated with the ablative stream whenreleased from the nozzle. Work in relation to embodiments has shown thatthe cavitating cloud can shed from the jet at a characteristic sheddingfrequency. A length 992 of each cloud is related to the sheddingfrequency and the velocity of the cloud. The relatively cool ablativeflame of the jet comprises a length 990 corresponding to the cuttinglength of the jet which can be adjusted to cut tissue to controlleddepth as described herein. In many embodiments, nozzle of the jet isplaced at least about a quarter of the length 992 of a shed cloud in annon-cutting configuration as shown in FIG. 5C, in order to allow theshedding cloud to substantially form prior to the cloud striking tissue.This divergence of the shed cloud to a larger cross sectional size canalso provide improved tissue removal as the cloud can be distributed toa larger region of tissue and provide improved overlap among the pulsesof the jet.

In addition to the impact pressure of the jet, the highly turbulent andaggressive region corresponding to the white cloud of the imagecontributes substantially to the ablation of tissue as described herein.The white cloud comprises a plurality of cavitation regions. Whenpressurized water is injected into water, small cavitations aregenerated in areas of low pressure in the shear layer, near the nozzleexit. The small cavitations may comprise cavitation vortices. Thecavitation vortices merge with one another, forming large discretecavitation structures that appear in the high speed images as cavitationclouds. These cavitation clouds provide effective ablation wheninteracting with tissue. Without being bound by any particular theory,it is believed that the cavitation clouds striking tissue causesubstantial erosion of tissue related to the cavitations in combinationof the high velocity fluid that defines the cavitations striking tissue.

The nozzle and pressure as described herein can be configured to providethe pulsatile clouds, for example with control of the angle of thenozzle, by a person of ordinary skill on the art based on the teachingsprovided herein. In many embodiments, the nozzle of the fluid deliveryelement comprises a cavitating jet in order to improve ablation oftissue.

The fluid delivery element nozzle and pressure can be arranged toprovide a shedding frequency suitable for removal of tissue.

In many embodiments, the “white cloud” of “flame” comprises an“entrainment” region where surrounding water is drawn in or “entrained”into the jet. Work in relation to embodiments suggests that theentrainment of fluid can be related to the shedding frequency.

The shedding frequency and size of the cloud shed from the jet can beused to provide tissue ablation in accordance with embodiments. Theshedding frequency can be combined with the angular sweep rate of theprobe around the longitudinal axis to provide overlap of the locationswhere each cloud interacts with the tissue.

FIG. 5F shows a plurality of shedding pulses 995 and sweeping of theablative jet to provide smooth and controlled tissue erosion at aplurality of overlapping locations 997 in accordance with embodiments.This shedding frequency can be substantially faster than the pumpfrequency, when a pump is used, such that a plurality of shedding cloudsare provided for each pulse of the pulsatile pump. The sweep rate of theprobe can be related to shedding frequency to provide improved tissueremoval, for example with the shedding clouds configured to provideoverlapping pulses.

In many embodiments, the system comprises a pump having a frequency lessthan a frequency of the shedding pulses, in order to provide a pluralityof shedding pulses for each pulse of the pump. The pump can have a pulserate of at least about 50 Hz, for example within a range of about 50 Hzto about 200 Hz, and the shedding pulses comprise a frequency of atleast about 500 Hz, for example within a range from about 1 kHz to about10 kHz.

Although pulses of a pump are illustrated, similar scanning of pulsedclouds can be provided with a continuous flow pump.

While the nozzle can be configured in one or more of many ways, in manyembodiments the nozzle comprises a Strouhal number (hereinafter “St”)within a range from about 0.02 to about 0.3, for example within a rangefrom about 0.10 to about 0.25, and in many embodiments within a rangefrom about 0.14 to about 0.2.

In many embodiments, the Strouhal number is defined by:St=(Fshed)*(W)/U

where Fshed is the shedding frequency, W is the width of the cavitatingjet, and U is the velocity of the jet at the exit. A person of ordinaryskill in the art can modify nozzles as described herein in order toobtain shedding frequencies suitable for combination in accordance withembodiments described herein, and experiments can be conducted todetermine the cloud lengths and shedding frequencies suitable for tissueremoval.

The nozzle configurations providing plurality of shedding clouds aresuitable for use with one or more of the probes as described herein.

Referring again to FIG. 6C, based on the diagnostic results of thetissue of the organ to which the treatment apparatus 100 is delivered,the plurality of seeds 132 may have different dosages, distributions,and/or configurations so as to provide for localized targeted segmentaltreatment. For example, a treatment apparatus 100 with a greaterdistribution of radioactive seeds 132 on a first side than on a secondside may be used to treat tissue in a target organ where diseased tissueis asymmetrically distributed.

FIG. 9 shows a treatment apparatus 150 in accordance with embodiments.The treatment apparatus 150 comprises an apparatus 100 as describedherein comprising the radioactive substance 130. A second treatmentapparatus 160 without the radioactive substance is provided. The secondtreatment apparatus 160 comprises structures similar to apparatus 100but without the radioactive substance. The treatment apparatus 150comprises a device 170 to test for the presence of cancer in a sampleremoved during surgery. The treatment apparatus 150 may comprise a kit152 comprising the apparatus 100, the second apparatus 160 and thetesting device 170. The kit 152 can be provided to the physician as aconsumable or disposable kit, for example, comprising a sterileapparatus 100, a sterile apparatus 160 and device 170 which may or maynot be sterile.

The second treatment apparatus 160, although referred to as the secondtreatment apparatus, can be provided independently and separately, forexample. The apparatus 160 comprises many of the structures of theapparatus 100 as described herein. For example, the apparatus 160 maycomprise the structures of apparatus 100 but without the radioactivesubstance.

The testing device 170 can be configured in one or more of many ways andmay comprise one or more of many markers, such as antigen antibodycombinations configured to detect biomarkers of one or more types ofcancer. The treatment device 170 is configured to receive a sample froma surgical site of the patient as described herein and to process thesurgical site material while the patient remains on the treatmentsupport structure.

FIG. 10 shows apparatus 160 in accordance with embodiments. Apparatus160 comprises one or more of many structures similar to apparatus 100.However, apparatus 160 is provided without the radioactive substance 130as described herein. Apparatus 160 is configured to expand from narrowprofile configuration 106 to wide profile configuration 108, asdescribed herein. Apparatus 160 can be left in the patient for aplurality of days similarly to apparatus 100. Apparatus 160 may compriseelectrodes for electrocautery in the expanded profile configuration.

FIG. 11 shows apparatus 160 comprising expandable support 120 and anchor140 as described herein. Apparatus 160 can be provided without theradioactive substance 130 as described herein. Apparatus 160 can beexpanded from the narrow profile configuration 106 to the wide profileconfiguration 108 as described herein.

Apparatus 160 can be provided as an alternative to apparatus 100 asdescribed herein, for example when the results of testing indicate thatthe patient does not have cancer. Expandable support of structure 120can be injected with a non-radioactive substance such as saline, forexample.

Alternatively or in combination, apparatus 160 can be injected with aradioactive substance to treat cancer with inflation of expandablesupport 120, for example, as shown in FIG. 10.

FIG. 14A shows a treatment apparatus comprising a bladder drain port180, urine exit port 182, and inflation port 184 in a narrow profileconfiguration 106 in accordance with many embodiments. In the narrowprofile configuration, the anchor 140 can be advanced to the bladderneck of the patient and the expandable support 120 advanced to theresected prostate P. The bladder drain port 180 allows urine to flow outfrom the bladder B and exit the body through the urine exit port 182,via the y-connector 186. The y-connector 186 is also connected to theinflation port 184, which may comprise a Luer connector 188 that acceptsa syringe to help inflate the anchor 140 and expandable support 120simultaneously with saline.

FIG. 14B shows apparatus as in FIG. 14A in an expanded configuration 108in accordance with many embodiments. The anchor 140 and expandablesupport 120 may be inflated via the injection of saline through theinflation port 184. In the expanded configuration 108, the movement ofthe anchor 140 and expandable support 120 is inhibited, and theapparatus can be left in the patient for a plurality of days, asdescribed herein. When expanded, the anchor 140 is compressed againstthe bladder wall to help prevent the leak of urine from the bladder B tothe prostate P.

FIGS. 15A and 15B show a treatment apparatus 100 comprising a sub-layerballoon 190 and a treatment substance port 198 in an expandedconfiguration 108 in accordance with many embodiments. The sub-layerballoon 190 comprises an outer layer 192 and an inner layer 194,resulting in the creation of an inter-layer cavity 196. As shown in FIG.15A, the inter-layer cavity 196 may be filled with radioactive orchemotherapeutic substances via injection of said substances into thetreatment substance port 198. As shown in FIG. 15B, the inter-layercavity 196 may be filled with air or other fluid (e.g., hot treatmentfluid or steam) via injection of air or other fluid into the port 198.The inter-layer cavity 196 may be compartmentalized to allow forlocalized (non-uniform) diffusion across the layers 192, 194 as well.The outer layer 192 may be configured to inhibit dispersion ofradioactive treatment substances across the surface of the sub-layerballoon 190. Alternatively or in combination, the outer layer 192 may beconfigured to allow dispersion of treatment substances across thesurface of the sub-layer balloon 190. For example, the outer layer 192may comprise a material that allows uniform diffusion of the treatmentsubstance across the layer.

FIG. 16 shows a treatment apparatus 100 comprising a peripheralisolation balloon 200 in an expanded configuration 108 in accordancewith many embodiments. The expandable support 120 may compriseradioactive substances 130 and disperse said substances to thesurrounding tissue as described herein. The peripheral isolation balloon200 comprises an expandable structure positioned at the proximal end ofthe prostate P, and may be expanded simultaneously with the expansion ofthe anchor 140 and expandable support 120, for example. The expandedperipheral isolation balloon 200 can help prevent the radioactivesubstances from leaking into the urethra. Similarly, the expandedanchoring balloon 142 can help prevent the leak of radioactivesubstances into the bladder B. The use of either or both the anchoringballoon 142 and peripheral isolation balloon 200 can help improve thetargeting of the treatment while limiting the exposure of the body toradioactive material. The treatment may be targeted to differentlocations of the prostate by choosing balloons 200 of the treatmentapparatus 100 with varied permeability configurations or fenestrationpatterns.

FIGS. 17A1 and 17A2 show a treatment apparatus 100 comprisingradioactive pellets 202 in accordance with many embodiments. Theradioactive pellets 202 comprise a radioactive face 204 and a shieldingface 206 that shields radioactivity from the radioactive face 204. Thepellets 202 may further comprise a suture 208 that anchors the pelletsto the expandable support 120, which is expanded as shown in FIG. 17A1,and/or to the elongate tubular member 110, as shown in FIG. 17A2. Theradioactive side can be oriented toward the prostate capsule, and theshield side oriented away from the prostate tissue in order to shieldtissue away from the prostate capsule.

FIG. 17B shows the structure of radioactive pellets 202 and method forconfiguration in accordance with many embodiments. The pellets 202 areconfigured to be capable of penetrating tissue such as the prostatecapsule P, and of expanding once on the outside of the tissue, so thatthe radioactive face 204 of the pellets can contact the outside of thetissue. For example, a pellet may be collapsed such that the shieldingface 206 forms the exterior surface of the collapsed pellet; once thepellet has crossed the tissue, it can unfold such that the radioactiveface 204 contacts the tissue. The pellets 202 may further comprise thesuture 208 that allows the expanded pellet to the compressed inwards, sothat the radioactive face 204 forms optimal contact with the tissue.

FIG. 18 shows an expandable support 120 comprising one or more of aplurality of shapes in accordance with many embodiments. The expandablesupport can be shaped in one or more of many ways so as to conform tothe profile of resected tissue. In many embodiments, the expandablesupport comprises a free standing profile corresponding to the shape ofresected tissue. The support having free standing profile correspondingto the shape of the resected tissue can provide an improved fit to thetissue. The free standing profile may have a cross-sectional shape 121comprising one or more of circular 121 a, oval 121 b, triangular 121 cor semi-circular 121 d, for example.

FIG. 19 shows bipolar cautery electrodes 172 on an expandable support120 in accordance with many embodiments. The bipolar cautery electrodescan be located on the support in one or more of many ways. For example,the active electrode 174 can be located on an outer surface of theexpandable support and the return electrode 176 located on an innersurface of the expandable support. Alternatively or in combination, boththe active electrode and the return electrode may be connected to theactive line so that the expandable support may be changeable to amono-polar configuration. In many embodiments, the bipolar electrodescomprise a plurality of active electrode branches and a plurality ofreturn electrode branches, in which the active electrode branches aresubstantially interleaved with the return electrode branches.

The expandable support may comprise a balloon wall comprising one ormore of a high-temperature resistant elastomeric material.

The embodiments of FIG. 19 may comprise one or more structures of thebipolar electrodes on the support of the embodiments shown in FIG. 12 asdescribed herein, and vice versa.

FIG. 20 shows a method 300 of treating a patient in accordance withembodiments. At a step 310 the patient is diagnosed with havinghyperplasia at a location. The hyperplasia may comprise benignhyperplasia, such as benign prostate hyperplasia (BPH); alternatively,the hyperplasia may comprise a cancerous hyperplasia. In manyembodiments the patient is diagnosed as having the hyperplasia andsubjected to additional testing. The location of the patient where thehyperplasia is located may comprise a location of an organ, such as theprostate, the eye, the kidneys, or any other known organs, for example,the breast.

The patient is placed on a support at a step 320. The support can be oneor more of many objects that supports the patient. For example, a bed,stirrups, a chin rest or a head rest, for example. At a step 330 atreatment profile is defined. The treatment profile can be defined inone or more of many ways, and this step is optional. The treatmentprofile may comprise an image guided treatment profile to remove apre-defined amount of tissue from the organ in order to substantiallyremove the hyperplasic tissue. The treatment profile can be defined forremoval of material from inside the organ outwardly toward a capsule ofthe organ, for example.

At a step 340 tissue is removed from the location in accordance with theprofile. The tissue can be removed in one or more of many ways. Forexample, with mechanical scraping, abrading, a water jet, laserablation, radio frequency ablation, erosion with chemical processes incombinations thereof for example. In many embodiments the tissue isremoved without a predefined profile. For example, with visualobservation of the organ and removal of the tissue.

At a step 350 the removed tissue material is provided to a testingdevice. The testing device may comprise one or more of many devices asdisclosed herein.

At a step 360 the presence or absence of cancer is determined while thepatient remains on the support. This has the advantage of allowing thetreatment to be determined while the patient is in surgery and whileaccess to the surgical site is available.

At a step 370 a catheter is selected for placement in the patient at thelocation. The catheter may comprise the elongate tubular member andsupport structure as described herein. For example, the selectedcatheter may comprise the catheter having the radioactive substance orthe catheter without the radioactive substance.

At a step 380 the selected catheter is inserted into the patient. Theselected catheter can be inserted with the narrow profile configurationas described herein and expanded to the wide profile configuration asdescribed herein in order to engage tissue at the surgical site with theexpandable support.

At a step 390 the selected catheter remains in the patient for aplurality of days. The plurality of days may comprise a pre-determinednumber of days in accordance with a treatment plan. For example, theplurality of days may comprise a plurality of days to deliver aradiation therapy with a radioactive substance as described herein.Alternatively the plurality of days may comprise of a plurality of daysdetermined for a treatment catheter placed without a radioactivesubstance as described herein.

At a step 395 the catheter is removed.

Although the above steps show method 300 of treating a patient inaccordance with embodiments, a person of ordinary skill in the art willrecognize many variations based on the teaching described herein. Thesteps may be completed in a different order. Steps may be added ordeleted. Some of the steps may comprise sub-steps. Many of the steps maybe repeated as often as if beneficial to the treatment.

One or more of the steps of the method 300 may be performed with thecircuitry as described herein, for example one or more of the processoror logic circuitry such as the programmable array logic for fieldprogrammable gate array. The circuitry may be programmed to provide oneor more of the steps of method 600, and the program may comprise programinstructions stored on a computer readable memory or programmed steps ofthe logic circuitry such as the programmable array logic or the fieldprogrammable gate array, for example.

Diagnostic Test Apparatus

The diagnostic test apparatus 170 may comprise one or more of many knownor commercially available tests. In many embodiments, the one or moretumor markers comprise one or more tumor markers found on the canceritself, for example with the tissue collected from the surgicalprocedure. The apparatus may comprise multiplexing instruments. Theapparatus 170 may comprise one or more commercially available componentssuch as LabMAP components commercially available from Luminex(www.millipore.com) or Environic ChemPro 100 eNose, which can examineand discriminate prostate cancer by analysis of urine headspace. Insteadof urine, the apparatus 170 may be exposed to resected aspirate fluid(non-contact) in a chamber that would allow for detection via air. Theapparatus 170 may comprise components to test for one or more of thefollowing markers:

Adipokines

-   -   TNF-RI    -   TNF-RII    -   Leptin    -   TNFa    -   VEGF    -   Adiponectin    -   Resistin

Immune Response

-   -   IL-2R    -   sIL-6R    -   MIF    -   IL    -   IL-6    -   G-CSF    -   IL-1Ra    -   MPO    -   MIP-1    -   MCP-1a    -   sE-Selectin    -   IP-10

Metalloproteinases

-   -   MMP-2    -   MMP-3    -   MMP-9    -   PAI-1 (active)    -   tPAI-1

Adhesion

-   -   SVCAM-1    -   SICAM-1

Hormones, Growth Factors

-   -   FSH    -   LH    -   Prolactin    -   TSH    -   Adrenocorticorticotropic hormone    -   GH    -   IGFBP-1

Tumor Markers

-   -   HCG    -   AFP    -   aKallikrein_10    -   Carcinoembryonic antigen    -   CA-125    -   CA 15-3    -   CA 19-9    -   CA 72_4    -   Kallikrein_8    -   Mesothelin

Growth and Tumor Markers

-   -   EGFR    -   EGF    -   TGFa    -   HGF    -   NGF    -   ErbB2

Other

-   -   FAS_L    -   Fractalkine    -   EOTAXIN    -   Cytokeratin_19    -   Fas

Components for testing such markers are commercially available asdescribed in “Assessment of 54 Biomarkers for Biopsy-Detectable ProstateCancer”, Parekh et al., Cancer Epidemiology Biomarkers and Prevention.

The treatment apparatus 100 described herein may be used to detect andlocalize cancer in real-time. The treatment apparatus 100 may be used incombination with the diagnostic test apparatus 170 to detect andlocalize cancer in real time. The cancer can be identified when thepatient remains on the support, and suitable treatment determined forexample. The diagnostic testing and corresponding identification of thecancer can be real time, or within about 5 minutes, for example.

FIG. 21A shows the treatment apparatus 100 placed in the urethra U of apatient to reach the bladder. The treatment apparatus 100 may bethreaded along or through a handpiece 210 which may comprise a pluralityof aspiration ports 220 distributed along the length of the distalportion of the handpiece 210. As shown in FIGS. 21A and 21B, thetreatment apparatus 100 may be retracted proximally in the directionindicated by arrow 201 (e.g., the distal tip of the treatment apparatus100 may be retracted from the bladder toward the penis) to remove tissuefrom the base of the prostate P to the apex of the prostate such as witha liquid jet 101. As tissue is removed, the resected tissue may besuctioned through the aspiration ports 210.

The prostate P may be divided into cutting zones Z1, Z2, Z3, Z4, Z5, Z6,and Z7, for example. The zones Z1, Z2, Z3, Z4, Z5, Z6, and Z7 may besagittal zones and the treatment apparatus 100 (and the liquid jet 101)may be fully rotated as the apparatus 100 is retracted. The zones Z1,Z2, Z3, Z4, Z5, Z6, and Z7 may be transverse zones and the treatmentapparatus 100 (and the liquid jet 101) may be partially rotated as theapparatus 100 is retracted. As the treatment apparatus 100 begins to cutin zone Z1 toward zone Z2, the aspirate may be analyzed in real-time inzone Z1 to determine the presence of cancer. The analysis can continuein zone Z2, Z3, and so on so as to locate the source(s) of cancer withinthe prostate.

The presence of cancerous cells can be detected in many ways. Opticalabsorption and scattering may be used to detect higher bloodconcentration and lower oxygen level characteristics of cancerous cells.Fluorescence spectroscopy may be used to detect the different molecularcomposition of cancerous cells or even pre-cancerous cells. Opticalcoherence domain reflectometry may be used to detect structural changesand patterns in cellular architecture which may be characteristic ofcancerous cells. Fluorescence microscopy may also be used to imageresected tissue sections to visualize and semi-quantitatively analyzethe distribution of cancerous cells. For example, resected tissuesections may be treated with a photodynamic agent known to accumulate intumor tissue, such as 5-aminolevulinic acid (5-ALA). 5-ALA can induceprotoporphyrin IX (PPIX), which fluoresces in tissue and can thus bevisualized via fluorescence microscopy. Fluorescence images may bedigitized and their fluorescence intensity quantified, in order tosemi-quantitatively analyze the distribution of cancerous cells. Thesedetection methodologies are examples only and may be used alone, incombination with one another, or in combination with further cancer celldetection methodologies. An example of cancer diagnosis using lightscatter is described in “Early diagnosis of cancer using light scatterspectroscopy,” Backman, V., Massachusetts Institute of Technology, 2001.

The division of the prostate P into 7 cutting zones is for example only.Different numbers of divisions of the prostate P may be used. Forexample, a zone Z1 may be divided into two or more zones based on thedepth of the tissue in relation to the apparatus 100 (see zones Z1A,Z1B, and Z1C shown in FIG. 21C) and/or or based on radial location (seezones Z1X, Z1Y, and Z1Z shown in FIG. 21D).

By identifying the location of the cancer within the prostate P, therapymay be targeted rather than homogenous. Homogenous treatment may resultin excess and unwanted collateral damage to neighboring tissues,vessels, nerve, as well as remaining non-cancerous prostatic tissue. Thetreatment may be adapted and dosed to reflect the severity of cancerbetween the different zones of the prostate P. Cancer treatment dosagecan be determined real-time base on the real-time diagnostic testingdescribed above. Dosage may be adjusted based on degree/state of cancerfor entire prostate or may be adjusted for each prostate zone asillustrated in FIGS. 21A to 21D. The prostate may be diagnosed andtreated in segments. As described herein, the apparatus 100 may beprovided with balloon(s) and/or seeds which may allow for targetedsegmental treatment.

As disclosed herein, the apparatus may comprise multiplexinginstruments. The apparatus 170 may comprise one or more commerciallyavailable components such as LabMAP components commercially availablefrom Luminex (www.millipore.com) or Environic ChemPro 100 eNose, whichcan examine and discriminate prostate cancer by analysis of urineheadspace. Instead of urine, the apparatus 170 may be exposed toresected aspirate fluid (non-contact) in a chamber that would allow fordetection via air.

EXPERIMENTAL

FIG. 22 shows maximum tissue penetration depth of cutting and flow ratethrough a nozzle in accordance with embodiments. The maximum penetrationdepth corresponds substantially to the length of the cavitation bubblesof the jet comprising the “cold” aquablation flame. The maximum tissuepenetration depth of ablation corresponds directly to the flow rate andin many embodiments is linearly related to the flow rate.

The inset of FIG. 22 shows cut potato as a model of prostate BPH, inaccordance with embodiments. The maximum penetration depth of potatocorresponds closely to the maximum cut depth of BPH. The potato is showncut with 10 different flow settings corresponding to rates within arange from about 50 ml/min to about 250 ml/min with a nozzle androtating probe as described herein. The maximum penetration depth rangesfrom about 4 mm at 50 ml/min to about 20 mm at about 250 ml/min.

In many embodiments, the cavitation cloud growth and length comprises afunction of flow rate, which is proportional to the injection pressureand vice versa, for an appropriately configured nozzle as describedherein. As the pressure increases, the maximum erosive radius appears toincrease linearly, which is shown as the maximum penetration depth ofFIG. 22.

High velocity cavitating jets can be created by using an known highpressure pump to force the water through a nozzle in either a continuousor pulsatile flow. Despite the flow type produced by a pump, thecavitation phenomenon will be pulsatile due to the unsteady nature ofvapor cavities and the cavity formation will be pulsatile even in acontinuous flow jet as described herein. Without being bound to aparticular theory, it is believed that both pulsatile and continuousflow waterjets will result in equivalent amounts of material erosionover a given amount of time. In many embodiments, nozzle geometry isconfigured to provide the flow dynamics and cavitation process asdescribed herein. In many embodiments, the nozzle is configured toinhibit tight constriction at the waterjet exit, which can be relatedcavitation can occur inside the nozzle itself. In many embodiments, thesharp corners cause the water to separate from the wall and convergetowards the nozzle centerline, further constricting the waterjet pathwaywhile simultaneously reducing frictional effects caused by the nozzlewall. This results in an increased velocity along with the correspondingpressure drop and the vapor cavities formation. Vapor cavity formationwill impact the overall flow dynamics as their eventual collapse resultsin turbulence and can affect erosion depth. A person of ordinary skillin the art can conduct experiments to determine appropriate nozzlegeometry and flow rate to provide tissue removal as described hereinwithout undue experimentation.

Aquablation

Submerged waterjet cutting as described herein has the capability totake advantage of the cavitation phenomenon to treat patients withBenign Prostatic Hyperplasia (BPH). The jet removes the excess softtissue growth seen in BPH through the pressure pulses and microjetscaused by collapsed vapor cavities. The waterjet direction can bemanipulated by changing the location and orientation of the devicesnozzle, either by translating the nozzle along the anterior-posteriordirection or by rotating the nozzle up to 180 degrees, for example.

As vapor cavity formation and its erosive strength is a function of bothinjection pressure and the flow dynamics, the depth of material can becontrolled by configuring the pressure as well as nozzle geometry. Agreater injection pressure will result in a faster exit velocity. Asdiscussed herein, the nozzle geometry can further increase the velocitydepending on the constriction and will affect the degree of pressuredrop as the waterjet exits through the Venturi effect. These factors canresult in longer distances the cavitation clouds can grow to and travelbefore collapsing and releasing pressure pulses and microjets. Thenozzle geometry and pressure settings of the Aquablation system havebeen optimized to give the user precise control and ensure thecavitating jet removes only the desired benign tissue growth.

The images provided herein show the how tissue erosion depth is afunction of pressure, in accordance with embodiments. The images showthe smaller cavitation cloud length and corresponding tissue resectiondepth for a lower injection pressure as compared with other images.

In many embodiments, Aquablation as described herein is capable ofremoving the excess tissue growth, e.g. BPH, with inhibited removal anddamage of arteries and veins. The pressure pulses and microjets causedby cavitation exceed the threshold energy required to erode the softtissue growth, and may cause minimal damage to other structures likevessels which have a much higher threshold energy. Repeated andconcentrated pressure pulses and microjets may cause fatigue stress onthe vasculature and result in bleeding, but the Aquablation systemalgorithm and treatment instructions as described herein are configureddesigned to inhibit such damage.

In many embodiments, generation of harmful emboli are inhibited. Vaporcavity formation may benefit from a minute nucleus of air alreadypresent in the blood stream, for example. Cavitation can result in thegrowth of the nucleus without any additional air being introduced intothe system. Furthermore, the cavity will collapse once the local jetpressure exceeds the vapor pressure, such that the air pockets mayreduce back to their original nucleus size. In many embodiments, embolusformation is inhibited as cavitation depends on and can be limited tomicro amounts of air native to the saline solution surrounding theurethra, and the vapor cavities quickly dissipate as the jet pressurebegins to rise.

Aquablation as described herein takes advantage of this phenomenon. Thenaturally self-limiting erosive radius and unique ability to preciselyablate tissue with a low damage threshold energy while minimizing damageto nearby structures with a more dense cellular structure, such asarteries, make Aquablation as described herein a useful surgical toolfor treating BPH. Coupled with the nearly isothermal property ofcavitation as described herein, which can mitigate collateral damage andprovide improved healing and an improved safety profile.

FIG. 23 shows selective removal of potato with a porcine blood vesselpositioned over the incision of the potato as a model for selectiveremoval of tissue. The porcine blood vessel was placed on the potatoprior to the incision, such that the porcine blood vessel was exposed tothe water jet with cavitation in order to remove the potato. Aquablationresected the soft potato tissue model, which is a close proxy for thebenign tissue growth seen in BPH, without causing severe damage to theporcine vessel.

While preferred embodiments of the present disclosure have been shownand described herein, it will be obvious to those skilled in the artthat such embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will be apparent to those skilledin the art without departing from the scope of the present disclosure.It should be understood that various alternatives to the embodiments ofthe present disclosure described herein may be employed withoutdeparting from the scope of the present invention. Therefore, the scopeof the present invention shall be defined solely by the scope of theappended claims and the equivalents thereof.

What is claimed is:
 1. A method of treating a patient, the method comprising: placing the patient on a support; removing a sample of a tissue from the patient using a water jet source while the patient is on the support; placing, while the patient is on the support, a first catheter or a second catheter in the patient subsequent to removing the sample, the first catheter comprising a radioactive substance to treat a cancer of the patient subsequent to surgery, the second catheter without the radioactive substance for cancer treatment; and receiving the sample using a device; and determining using the device, while the patient is on the support, whether the patient has the cancer in order to select the first catheter or the second catheter for placement in the patient.
 2. The method of claim 1, comprising: using the first catheter comprising the radioactive substance to treat the cancer of the patient subsequent to surgery.
 3. The method of claim 1, comprising: using the second catheter without the radioactive substance to treat the patient subsequent to surgery.
 4. The method of claim 1, comprising: determining a presence of the cancer in each of a plurality of zones of a prostate, in order to select the first catheter or the second catheter for placement into said each of the plurality of zones of the prostate.
 5. The method of claim 1, wherein the selected first or second catheter is configured to be inserted into the patient's body with a narrow profile configuration and to expand to a wide profile configuration to engage tissue at a surgical site of the patient.
 6. The method of claim 1, wherein the selected first or second catheter is configured to remain in the patient's body for a predetermined number of days.
 7. The method of claim 1, wherein the selected first catheter is configured to be inserted into the patient's body with a narrow profile configuration and to expand to a wide profile configuration to place the first catheter against tissue within the patient's body to treat the tissue within the patient's body with the radioactive substance.
 8. The method of claim 1, wherein the selected second catheter is configured to be inserted into the patient's body with a narrow profile configuration and to expand to a wide profile configuration to place the second catheter against tissue within the patient's body to treat the tissue within the patient's body without the radioactive substance.
 9. The method of claim 1, wherein the first catheter comprises a first elongate tubular member and a first expandable support for insertion into the patient and the second catheter comprises a second elongate tubular member and a second expandable support.
 10. The method of claim 1, wherein, the first catheter or the second catheter is placed in the patient with the patient on the support.
 11. The method of claim 1, wherein the determining whether the patient has cancer comprises one or more of testing for optical absorption and scattering on the tissue, performing fluorescence spectroscopy on the tissue, or performing optical coherence domain reflectometry on the tissue.
 12. The method of claim 1, wherein determining whether the patient has cancer comprises determining whether the tissue comprises cancer tissue in real-time concurrently with removing the tissue.
 13. The method of claim 1, wherein determining whether the patient has cancer further comprises determining whether the tissue comprises pre-cancerous tissue. 